Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts
Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts
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DOI：
10.1016/j.cardiores.2005.03.008
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发表时间：
2005-07-01
影响因子：
10.8
通讯作者：
Kass, DA
中科院分区：
文献类型：
--
作者：
Spragg, DD;Akar, FG;Kass, DA
背景资料：由于心室内传导延迟引起的心脏不同步性在衰竭心脏中产生不均匀的局部室壁应力和心律失常易感性。我们研究是否慢性不同步本身诱导区域异质性电生理remodel.Methods和结果：成年狗（n=9）进行左束支分支射频消融（QRS波持续时间从50 - 7增加到104 +/- 7毫秒）; 6未处理的狗作为对照。消融（n=3）和对照（n=4）犬的一个子集接受标记的MR成像，以确认消融诱导的左心室（LV）不同步。四周后，心脏被切除，早期（前）和晚期（侧）激活的心肌节段被分离。通过细胞外标测和光学标测研究起搏、动脉灌注心肌楔的传导速度（CV）、动作电位时程（APD）和不应期（RP），并通过程序刺激评估心律失常易感性。区域应力反应激酶，钙循环，和间隙连接蛋白的表达通过Western印迹法测定，和连接蛋白43的亚细胞分布通过免疫荧光显微镜分析。与前壁相比，不同步心脏的晚激动侧壁的CV、APD和RP显著降低。在不同步的外侧LV中，CV的正常差异（心内膜>心外膜）被逆转。虽然在不同步模型中连接蛋白43的总表达没有改变，但其亚细胞位置在晚期激活的心肌中从闰盘重新分布到外侧肌细胞膜。正常和不同步模型的组织中心律失常罕见。钙循环蛋白（肌浆网Ca 2 +-ATP酶和受磷蛋白）和应激反应激酶磷酸化ERK的总表达没有变化区域在任何model.Conclusions：不同步，即使在没有LV功能障碍诱导区域特异性的变化，传导和复极。这些变化支持了一种新的机制，将机械不同步与持续的电生理重塑和异质性联系起来。(c)2005年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Background: Cardiac dyssynchrony due to intraventricular conduction delay produces heterogeneous regional wall stress and worsens arrhythmia susceptibility in failing hearts. We examined whether chronic dyssynchrony per se induces regionally heterogeneous electrophysiological remodeling.Methods and results: Adult dogs (n=9) underwent left bundle branch radiofrequency ablation (QRS duration increased from 50 7 to 104 +/- 7 ms); 6 untreated dogs served as controls. A subset of ablated (n=3) and control (n=4) dogs underwent tagged MR imaging to confirm ablation-induced left ventricular (LV) dyssynchrony. Four weeks later, hearts were excised and early (anterior)- and late (lateral)-activated myocardial segments were isolated. Conduction velocity (CV), action potential duration (APD), and refractory period (RP) of paced, arterially perfused myocardial wedges were studied by extracellular and optical mapping, and arrhythmia susceptibility was assessed by programmed stimulation. Regional stress-response kinase, calcium cycling, and gap junction protein expression were assayed by Western blotting, and the subcellular distribution of connexin43 was analyzed by immunofluorescence microscopy. CV, APD, and RP were significantly reduced in the late-activated, lateral wall of dyssynchronous hearts compared to the anterior wall. Normal differences in CV (endocardial > epicardial) were reversed in the dyssynchronous lateral LV. While the total expression of connexin43 was unaltered in dyssynchronous models, its subcellular location was redistributed in late-activated myocardium from intercalated discs to lateral myocyte membranes. Arrhythmias were rare in tissue from normal and dyssynchronous models. Total expression of calcium-cycling proteins (sarcoplasmic reticulum Ca2+-ATPase and phospholamban) and the stress-response kinase phospho-ERK did not vary regionally in either model.Conclusions: Dyssynchrony even in the absence of LV dysfunction induces regionally specific changes in conduction and repolarization. These changes support a novel mechanism linking mechanical dyssynchrony to persistent electrophysiological remodeling and heterogeneity. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.